PTHSL2
MCID: PTT030
MIFTS: 41

Pitt-Hopkins-Like Syndrome 2 (PTHSL2)

Categories: Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Pitt-Hopkins-Like Syndrome 2

MalaCards integrated aliases for Pitt-Hopkins-Like Syndrome 2:

Name: Pitt-Hopkins-Like Syndrome 2 57 12 72 29 13 6 15 39 70
Pthsl2 57 12 72
Mesh; D006985 72
Mesh; D008607 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
three patients have been reported (as of february 2012)


HPO:

31
pitt-hopkins-like syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Pitt-Hopkins-Like Syndrome 2

UniProtKB/Swiss-Prot : 72 Pitt-Hopkins-like syndrome 2: A syndrome characterized by severe mental retardation and variable additional symptoms, such as impaired speech development, autistic behavior, breathing anomalies and a broad mouth, resembling Pitt- Hopkins syndrome. Other features include decreased reflexes in the upper extremities, constipation, strabismus, and protruding tongue with drooling. In contrast to patients with Pitt-Hopkins syndrome, PTHSL2 patients present with normal or only mildly to moderately delayed motor milestones.

MalaCards based summary : Pitt-Hopkins-Like Syndrome 2, also known as pthsl2, is related to pitt-hopkins-like syndrome 1 and pitt-hopkins-like syndrome, and has symptoms including constipation and breath-holding spell. An important gene associated with Pitt-Hopkins-Like Syndrome 2 is NRXN1 (Neurexin 1), and among its related pathways/superpathways are Cell adhesion molecules and Protein-protein interactions at synapses. Affiliated tissues include tongue, and related phenotypes are epileptic encephalopathy and broad-based gait

Disease Ontology : 12 A syndromic intellectual disability characterized by developmental delay and intellectual disability with many patients also displaying infantile hypotonia and autistic features that has material basis in compound heterozygous or homozygous mutation in NRXN1 on chromosome 2p16.3.

More information from OMIM: 614325

Related Diseases for Pitt-Hopkins-Like Syndrome 2

Diseases in the Pitt-Hopkins Syndrome family:

Pitt-Hopkins-Like Syndrome 1 Pitt-Hopkins-Like Syndrome 2
Pitt-Hopkins-Like Syndrome

Diseases related to Pitt-Hopkins-Like Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
# Related Disease Score Top Affiliating Genes
1 pitt-hopkins-like syndrome 1 31.7 NRXN3 NRXN1 NLGN4X
2 pitt-hopkins-like syndrome 30.7 NRXN1 LOC114827832
3 pitt-hopkins syndrome 11.4
4 atypical autism 10.1 NRXN1 NLGN4X
5 leukodystrophy, hypomyelinating, 11 10.1 TANGO2 MIPEP
6 echolalia 10.1 NRXN1 NLGN4X
7 phelan-mcdermid syndrome 10.0 NRXN1 NLGN4X
8 tic disorder 10.0 NRXN1 NLGN4X
9 specific language impairment 9.9 NRXN1 NLGN4X
10 childhood disintegrative disease 9.9 NRXN3 NRXN1 NLGN4X
11 kaufman oculocerebrofacial syndrome 9.9 NRXN3 NRXN1 NLGN4X
12 kagami-ogata syndrome 9.8 NRXN3 NRXN1 NLGN4X
13 specific developmental disorder 9.8 NRXN3 NRXN1 NLGN4X
14 pervasive developmental disorder 9.8 NRXN3 NRXN1 NLGN4X
15 partington x-linked mental retardation syndrome 9.8 ZNF674 ZNF526
16 fragile x syndrome 9.7 NRXN3 NRXN1 NLGN4X
17 syndromic x-linked intellectual disability 9.6 ZNF674 ZNF41 NLGN4X
18 autosomal dominant non-syndromic intellectual disability 4 9.6 ZNF674 ZNF526 ZNF41
19 autosomal dominant non-syndromic intellectual disability 5 9.6 ZNF674 ZNF526 ZNF41
20 syndromic x-linked intellectual disability siderius type 9.6 ZNF674 ZNF526 ZNF41
21 non-syndromic x-linked intellectual disability 9.4 ZNF674 ZNF526 ZNF41 NLGN4X

Graphical network of the top 20 diseases related to Pitt-Hopkins-Like Syndrome 2:



Diseases related to Pitt-Hopkins-Like Syndrome 2

Symptoms & Phenotypes for Pitt-Hopkins-Like Syndrome 2

Human phenotypes related to Pitt-Hopkins-Like Syndrome 2:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 epileptic encephalopathy 31 frequent (33%) HP:0200134
2 broad-based gait 31 occasional (7.5%) HP:0002136
3 scoliosis 31 HP:0002650
4 constipation 31 HP:0002019
5 developmental regression 31 HP:0002376
6 gastroesophageal reflux 31 HP:0002020
7 intellectual disability, severe 31 HP:0010864
8 strabismus 31 HP:0000486
9 wide mouth 31 HP:0000154
10 protruding tongue 31 HP:0010808
11 pulmonic stenosis 31 HP:0001642
12 feeding difficulties 31 HP:0011968
13 generalized hypotonia 31 HP:0001290
14 drooling 31 HP:0002307
15 hyperventilation 31 HP:0002883

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Spine:
scoliosis

Head And Neck Eyes:
strabismus

Respiratory:
hyperventilation
breath-holding spells

Neurologic Behavioral Psychiatric Manifestations:
behavioral abnormalities
autistic features
self-harming behaviors

Neurologic Peripheral Nervous System:
hyporeflexia in the upper limbs

Abdomen Gastrointestinal:
constipation
gastroesophageal reflux
poor feeding

Head And Neck Mouth:
protruding tongue
drooling
broad mouth

Neurologic Central Nervous System:
hypotonia
mental retardation, severe
developmental regression after the first year
epileptic encephalopathy (in 2 of 3 patients)
broad-based gait (1 patient)
more
Cardiovascular Heart:
pulmonary stenosis

Endocrine Features:
early-onset puberty (in 2 of 3 patients)

Clinical features from OMIM®:

614325 (Updated 05-Apr-2021)

UMLS symptoms related to Pitt-Hopkins-Like Syndrome 2:


constipation; breath-holding spell

Drugs & Therapeutics for Pitt-Hopkins-Like Syndrome 2

Search Clinical Trials , NIH Clinical Center for Pitt-Hopkins-Like Syndrome 2

Genetic Tests for Pitt-Hopkins-Like Syndrome 2

Genetic tests related to Pitt-Hopkins-Like Syndrome 2:

# Genetic test Affiliating Genes
1 Pitt-Hopkins-Like Syndrome 2 29 NRXN1

Anatomical Context for Pitt-Hopkins-Like Syndrome 2

MalaCards organs/tissues related to Pitt-Hopkins-Like Syndrome 2:

40
Tongue

Publications for Pitt-Hopkins-Like Syndrome 2

Articles related to Pitt-Hopkins-Like Syndrome 2:

(show all 14)
# Title Authors PMID Year
1
Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters. 6 57
21964664 2011
2
CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. 57 6
19896112 2009
3
Mutation analysis of the NRXN1 gene in autism spectrum disorders. 6
28289584 2016
4
RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism. 6
26742492 2016
5
Rare copy number variants are common in young children with autism spectrum disorder. 6
25661985 2015
6
A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion. 6
25614873 2014
7
Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis. 6
25149956 2014
8
Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature. 6
23533028 2013
9
Investigation of NRXN1 deletions: clinical and molecular characterization. 6
23495017 2013
10
Molecular analysis of a deletion hotspot in the NRXN1 region reveals the involvement of short inverted repeats in deletion CNVs. 6
23472757 2013
11
Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions. 6
22617343 2012
12
Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1. 6
21827697 2011
13
Phenotypic spectrum of NRXN1 mono- and bi-allelic deficiency: A systematic review. 61
30873608 2020
14
A new case of Pitt-Hopkins-like syndrome 2? 61
28343708 2019

Variations for Pitt-Hopkins-Like Syndrome 2

ClinVar genetic disease variations for Pitt-Hopkins-Like Syndrome 2:

6 (show top 50) (show all 621)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NRXN1 NRXN1, 180-KB DEL, EX1-4 Deletion Pathogenic 9040 GRCh37:
GRCh38:
2 NRXN1 NM_001330078.2(NRXN1):c.2936C>G (p.Ser979Ter) SNV Pathogenic 9041 rs267606922 GRCh37: 2:50723177-50723177
GRCh38: 2:50496039-50496039
3 NRXN1 NRXN1, 79-KB DEL Deletion Pathogenic 30096 GRCh37:
GRCh38:
4 NRXN1 NRXN1, 287-KB DEL Deletion Pathogenic 30097 GRCh37:
GRCh38:
5 NRXN1 and overlap with 2 gene(s) NC_000002.12:g.(?_50465422)_(51032054_?)del Deletion Pathogenic 539893 GRCh37: 2:50692560-51259192
GRCh38: 2:50465422-51032054
6 NRXN1 NC_000002.12:g.(?_50053251)_(50055064_?)del Deletion Pathogenic 539897 GRCh37: 2:50280389-50282202
GRCh38: 2:50053251-50055064
7 NRXN1 NC_000002.12:g.(?_50528605)_(50553045_?)del Deletion Pathogenic 584283 GRCh37: 2:50755743-50780183
GRCh38: 2:50528605-50553045
8 overlap with 3 genes Deletion Pathogenic 560146 GRCh37: 2:50516550-51259738
GRCh38: 2:50289412-51032600
9 NRXN1 NC_000002.12:g.(?_50921849)_(51032054_?)del Deletion Pathogenic 654673 GRCh37: 2:51148987-51259192
GRCh38: 2:50921849-51032054
10 NRXN1 NC_000002.12:g.(?_50538233)_(50553045_?)del Deletion Pathogenic 656843 GRCh37: 2:50765371-50780183
GRCh38: 2:50538233-50553045
11 NRXN1 NM_001330078.2(NRXN1):c.3876del (p.Phe1293fs) Deletion Pathogenic 661438 rs1573629114 GRCh37: 2:50280661-50280661
GRCh38: 2:50053523-50053523
12 NRXN1 NC_000002.12:g.(?_51026351)_(51032054_?)del Deletion Pathogenic 584106 GRCh37: 2:51253489-51259192
GRCh38: 2:51026351-51032054
13 NRXN1 NC_000002.12:g.(?_50620002)_(50623635_?)del Deletion Pathogenic 831017 GRCh37: 2:50847140-50850773
GRCh38:
14 NRXN1 NC_000002.12:g.(?_50620002)_(51032054_?)del Deletion Pathogenic 832928 GRCh37: 2:50847140-51259192
GRCh38:
15 NRXN1 NM_001330078.2(NRXN1):c.3442C>T (p.Arg1148Ter) SNV Pathogenic 947115 GRCh37: 2:50464031-50464031
GRCh38: 2:50236893-50236893
16 NRXN1 NM_001330078.2(NRXN1):c.730_735delinsCTGG (p.Asp244fs) Indel Pathogenic 970430 GRCh37: 2:51254677-51254682
GRCh38: 2:51027539-51027544
17 NRXN1 NM_001330078.2(NRXN1):c.-59_772+1193del Deletion Pathogenic 976336 GRCh37: 2:51253447-51255470
GRCh38: 2:51026309-51028332
18 NRXN1 NM_001330078.2(NRXN1):c.4264G>T (p.Glu1422Ter) SNV Pathogenic 1027716 GRCh37: 2:50149342-50149342
GRCh38: 2:49922204-49922204
19 NRXN1 NM_001330078.2(NRXN1):c.772+1128_772+1129del Deletion Likely pathogenic 1048082 GRCh37: 2:51253511-51253512
GRCh38: 2:51026373-51026374
20 NRXN1 NM_001330078.2(NRXN1):c.1135-2A>G SNV Likely pathogenic 862655 GRCh37: 2:50848389-50848389
GRCh38: 2:50621251-50621251
21 NRXN1 NM_001330078.2(NRXN1):c.832+1G>A SNV Likely pathogenic 859935 GRCh37: 2:51149006-51149006
GRCh38: 2:50921868-50921868
22 NRXN1 NC_000002.12:g.(?_50236769)_(50346969_?)dup Duplication Likely pathogenic 833283 GRCh37: 2:50463907-50574107
GRCh38:
23 NRXN1 NM_001330078.2(NRXN1):c.772+1133T>C SNV Likely pathogenic 569367 rs1476850082 GRCh37: 2:51253507-51253507
GRCh38: 2:51026369-51026369
24 NRXN1 NM_001330078.2(NRXN1):c.772+1032G>A SNV Conflicting interpretations of pathogenicity 336552 rs771759988 GRCh37: 2:51253608-51253608
GRCh38: 2:51026470-51026470
25 NRXN1 NM_001330078.2(NRXN1):c.4248G>A (p.Pro1416=) SNV Conflicting interpretations of pathogenicity 211693 rs151195816 GRCh37: 2:50149358-50149358
GRCh38: 2:49922220-49922220
26 NRXN1 NM_001330078.2(NRXN1):c.3012G>A (p.Lys1004=) SNV Conflicting interpretations of pathogenicity 93595 rs201118246 GRCh37: 2:50723101-50723101
GRCh38: 2:50495963-50495963
27 NRXN1 NM_001330078.2(NRXN1):c.4392T>C (p.His1464=) SNV Conflicting interpretations of pathogenicity 138546 rs112536447 GRCh37: 2:50149214-50149214
GRCh38: 2:49922076-49922076
28 NRXN1 NM_001330078.2(NRXN1):c.322C>T (p.Pro108Ser) SNV Conflicting interpretations of pathogenicity 93599 rs199784029 GRCh37: 2:51255090-51255090
GRCh38: 2:51027952-51027952
29 NRXN1 NM_001330078.2(NRXN1):c.2605C>A (p.Leu869Met) SNV Conflicting interpretations of pathogenicity 93592 rs201818223 GRCh37: 2:50724745-50724745
GRCh38: 2:50497607-50497607
30 NRXN1 NM_001330078.2(NRXN1):c.2533C>T (p.His845Tyr) SNV Conflicting interpretations of pathogenicity 206245 rs199784139 GRCh37: 2:50724817-50724817
GRCh38: 2:50497679-50497679
31 NRXN1 NM_001330078.2(NRXN1):c.600C>T (p.Gly200=) SNV Conflicting interpretations of pathogenicity 503668 rs201481698 GRCh37: 2:51254812-51254812
GRCh38: 2:51027674-51027674
32 NRXN1 NM_001330078.2(NRXN1):c.4254A>G (p.Pro1418=) SNV Conflicting interpretations of pathogenicity 129824 rs55923848 GRCh37: 2:50149352-50149352
GRCh38: 2:49922214-49922214
33 NRXN1 NM_001330078.2(NRXN1):c.1365T>C (p.Leu455=) SNV Conflicting interpretations of pathogenicity 138549 rs201727684 GRCh37: 2:50780119-50780119
GRCh38: 2:50552981-50552981
34 NRXN1 NM_001330078.2(NRXN1):c.3489C>T (p.Ala1163=) SNV Conflicting interpretations of pathogenicity 378300 rs147580960 GRCh37: 2:50463984-50463984
GRCh38: 2:50236846-50236846
35 NRXN1 NM_001330078.2(NRXN1):c.3090A>C (p.Gly1030=) SNV Conflicting interpretations of pathogenicity 206207 rs201886024 GRCh37: 2:50699590-50699590
GRCh38: 2:50472452-50472452
36 NRXN1 NM_001330078.2(NRXN1):c.3219C>T (p.Asn1073=) SNV Conflicting interpretations of pathogenicity 129819 rs563089155 GRCh37: 2:50699461-50699461
GRCh38: 2:50472323-50472323
37 NRXN1 NM_001330078.2(NRXN1):c.105C>A (p.Gly35=) SNV Conflicting interpretations of pathogenicity 93584 rs55640811 GRCh37: 2:51255307-51255307
GRCh38: 2:51028169-51028169
38 NRXN1 NM_001330078.2(NRXN1):c.3201C>T (p.Ser1067=) SNV Conflicting interpretations of pathogenicity 206208 rs75275592 GRCh37: 2:50699479-50699479
GRCh38: 2:50472341-50472341
39 NRXN1 NM_001330078.2(NRXN1):c.772+1078A>G SNV Conflicting interpretations of pathogenicity 167389 rs144049982 GRCh37: 2:51253562-51253562
GRCh38: 2:51026424-51026424
40 NRXN1 NM_001330078.2(NRXN1):c.772+1040A>T SNV Conflicting interpretations of pathogenicity 206261 rs201741449 GRCh37: 2:51253600-51253600
GRCh38: 2:51026462-51026462
41 NRXN1 NM_001330078.2(NRXN1):c.4004C>T (p.Thr1335Ile) SNV Conflicting interpretations of pathogenicity 206281 rs200672080 GRCh37: 2:50280533-50280533
GRCh38: 2:50053395-50053395
42 NRXN1 NM_001330078.2(NRXN1):c.1978G>A (p.Ala660Thr) SNV Uncertain significance 206276 rs199939303 GRCh37: 2:50765556-50765556
GRCh38: 2:50538418-50538418
43 NRXN1 NM_001330078.2(NRXN1):c.1202C>T (p.Thr401Met) SNV Uncertain significance 206215 rs796052764 GRCh37: 2:50847278-50847278
GRCh38: 2:50620140-50620140
44 NRXN1 NM_001330078.2(NRXN1):c.1566C>T (p.Gly522=) SNV Uncertain significance 206220 rs199701804 GRCh37: 2:50779918-50779918
GRCh38: 2:50552780-50552780
45 NRXN1 NM_001330078.2(NRXN1):c.772+1081A>G SNV Uncertain significance 449074 rs759434607 GRCh37: 2:51253559-51253559
GRCh38: 2:51026421-51026421
46 NRXN1 NM_001330078.2(NRXN1):c.374A>G (p.Asn125Ser) SNV Uncertain significance 206238 rs770641207 GRCh37: 2:51255038-51255038
GRCh38: 2:51027900-51027900
47 NRXN1 NM_001330078.2(NRXN1):c.4236C>T (p.Gly1412=) SNV Uncertain significance 138544 rs587781101 GRCh37: 2:50149370-50149370
GRCh38: 2:49922232-49922232
48 NRXN1 NM_001330078.2(NRXN1):c.2459G>A (p.Ser820Asn) SNV Uncertain significance 206242 rs80293130 GRCh37: 2:50733671-50733671
GRCh38: 2:50506533-50506533
49 NRXN1 NM_001330078.2(NRXN1):c.262C>G (p.Arg88Gly) SNV Uncertain significance 206235 rs748684256 GRCh37: 2:51255150-51255150
GRCh38: 2:51028012-51028012
50 NRXN1 NM_001330078.2(NRXN1):c.600C>T (p.Gly200=) SNV Uncertain significance 503668 rs201481698 GRCh37: 2:51254812-51254812
GRCh38: 2:51027674-51027674

Expression for Pitt-Hopkins-Like Syndrome 2

Search GEO for disease gene expression data for Pitt-Hopkins-Like Syndrome 2.

Pathways for Pitt-Hopkins-Like Syndrome 2

Pathways related to Pitt-Hopkins-Like Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.51 NRXN3 NRXN1 NLGN4X
2
Show member pathways
10.91 NRXN3 NRXN1 NLGN4X
3 10.23 NRXN3 NRXN1

GO Terms for Pitt-Hopkins-Like Syndrome 2

Cellular components related to Pitt-Hopkins-Like Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 presynapse GO:0098793 8.8 NRXN3 NRXN1 NLGN4X

Biological processes related to Pitt-Hopkins-Like Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 learning GO:0007612 9.5 NRXN3 NRXN1 NLGN4X
2 social behavior GO:0035176 9.43 NRXN3 NRXN1 NLGN4X
3 presynaptic membrane assembly GO:0097105 9.4 NRXN1 NLGN4X
4 postsynaptic membrane assembly GO:0097104 9.37 NRXN1 NLGN4X
5 adult behavior GO:0030534 9.33 NRXN3 NRXN1 NLGN4X
6 neuron cell-cell adhesion GO:0007158 9.13 NRXN3 NRXN1 NLGN4X
7 vocalization behavior GO:0071625 8.8 NRXN3 NRXN1 NLGN4X

Molecular functions related to Pitt-Hopkins-Like Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor activity GO:0038023 9.33 NRXN3 NRXN1 NLGN4X
2 cell adhesion molecule binding GO:0050839 9.13 NRXN3 NRXN1 NLGN4X
3 neuroligin family protein binding GO:0097109 8.62 NRXN3 NRXN1

Sources for Pitt-Hopkins-Like Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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